75504-34-6

Basic information

• Product Name: TAMOXIFEN-N-OXIDE
• Synonyms: TAMOXIFEN-N-OXIDE;(Z)-2-[4-(1,2-Diphenyl-1-butenyl)phenoxy]-N,N-dimethylethanamine-N-oxide;Ethanamine, 2-(4-(1,2-diphenyl-1-butenyl)phenoxy)-N,N-dimethyl-, N-oxide, (Z)-;Tamoxifen epoxide;2-[4-[(1Z)-1,2-Diphenyl-1-buten-1-yl]phenoxy]-N,N-dimethylethanamine N-oxide
• CAS NO: 75504-34-6
• Molecular Formula: C₂₆H₂₉NO₂
• Molecular Weight: 387.51396
• Product Categories: Various Metabolites and Impurities;Intermediates & Fine Chemicals;Metabolites & Impurities;Pharmaceuticals;Protein Kinase Inhibitors and Activators;Aromatics;Nitric Oxide Reagents
• Mol File: 75504-34-6.mol
• Article Data: 6

Chemical Properties

• Appearance: /
• Storage Temp.: Hygroscopic, -20°C Freezer, Under Inert Atmosphere
• PKA: 4.49±0.40(Predicted)
• CAS DataBase Reference: TAMOXIFEN-N-OXIDE(CAS DataBase Reference)
• NIST Chemistry Reference: TAMOXIFEN-N-OXIDE(75504-34-6)
• EPA Substance Registry System: TAMOXIFEN-N-OXIDE(75504-34-6)

Safety Data

• Hazardous Substances Data: 75504-34-6(Hazardous Substances Data)

Usage

Description

TAMOXIFEN-N-OXIDE, also known as an N-oxide derived from tamoxifen, is a metabolite of tamoxifen with significant interest in the medical field. It is a white solid and possesses the chemical properties of an N-oxide. TAMOXIFEN-N-OXIDE is particularly noted for its role in the treatment of some forms of breast cancer due to its function as a nonsteroidal estrogen antagonist. Additionally, it exhibits properties as a Protein Kinase C inhibitor and has the ability to induce apoptosis in human malignant glioma cell lines.

Uses

Used in Pharmaceutical Industry:
TAMOXIFEN-N-OXIDE is used as a therapeutic agent for the treatment of some forms of breast cancer. As a nonsteroidal estrogen antagonist, it plays a crucial role in managing the disease by inhibiting the effects of estrogen, which can contribute to the growth of cancer cells.
TAMOXIFEN-N-OXIDE is also used as an anticancer agent in the treatment of human malignant glioma cell lines. It functions as a Protein Kinase C inhibitor, which helps in controlling the growth and spread of cancer cells. Furthermore, its ability to induce apoptosis contributes to the reduction of cancer cell populations.

InChI:InChI=1/C26H29NO2/c1-4-25(21-11-7-5-8-12-21)26(22-13-9-6-10-14-22)23-15-17-24(18-16-23)29-20-19-27(2,3)28/h5-18H,4,19-20H2,1-3H3/b26-25-

Upstream product

• 10540-29-1 tamoxifen 

Downstream Products

• 5725-96-2 N,N-dimethylhydroxylamine 
• 80234-19-1 (Z)-4-(1,2-diphenyl-1-butenyl)phenol vinyl ether 

Relevant articles and documents

Potential beneficial metabolic interactions between tamoxifen and isoflavones via cytochrome P450-mediated pathways in female rat liver microsomes

Purpose. This study aims to evaluate a cytochrome P450-based tamoxifen-isoflavone interaction and to determine the mechanisms responsible for inhibitory effects of isoflavones (e.g., genistein) on the formation of α-hydroxytamoxifen. Methods. Metabolism studies were performed in vitro using female rat liver microsomes. The effects of genistein and an isoflavone mixture on tamoxifen metabolism and the inhibition mechanism were determined using standard kinetic analysis, preincubation, and selective chemical inhibitors of P450. Results. Metabolism of tamoxifen was saturable with K m values of 4.9 ± 0.6, 14.6 ± 2.2, 25 ± 5.9 μM and Vmax values of 34.7 ± 1.4, 297.5 ± 19.2, 1867 ± 231 pmol min-1 mg-1 for α-hydroxylation, N-desmethylation, and N-oxidation, respectively. Genistein (25 μM) inhibited α-hydroxylation at 2.5 μM tamoxifen by 64% (p A combination of three (genistein, daidzein, and glycitein) to five isoflavones (plus biochanin A and formononetin) inhibited tamoxifen α-hydroxylation to a greater extent but did not decrease the formation of identified metabolites. The inhibition on α-hydroxylation by genistein was mixed-typed with a Ki , value of 10.6 μM. Studies using selective chemical inhibitors showed that tamoxifen α-hydroxylation was mainly mediated by rat CYP1A2 and CYP3A1/2 and that genistein 3'-hydroxylation was mainly mediated by rat CYP1A2, CYP2C6 and CYP2D1. Conclusions. Genistein and its isoflavone analogs have the potential to decrease side effects of tamoxifen through metabolic interactions that inhibit the formation of α-hydroxytamoxifen via inhibition of CYP1A2.

Human flavin-containing monooxygenase 1 and its long-sought hydroperoxyflavin intermediate

Out of the five isoforms of human flavin-containing monooxygenase (hFMO), FMO1 and FMO3 are the most relevant to Phase I drug metabolism. They are involved in the oxygenation of xenobiotics including drugs and pesticides using NADPH and FAD as cofactors. Majority of the characterization of these enzymes has involved hFMO3, where intermediates of its catalytic cycle have been described. On the other hand, research efforts have so far failed in capturing the same key intermediate that is responsible for the monooxygenation activity of hFMO1. In this work we demonstrate spectrophotometrically the formation of a highly stable C4a-hydroperoxyflavin intermediate of hFMO1 upon reduction by NADPH and in the presence of O2. The measured half-life of this flavin intermediate revealed it to be stable and not fully re-oxidized even after 30 min at 15 °C in the absence of substrate, the highest stability ever observed for a human FMO. In addition, the uncoupling reactions of hFMO1 show that this enzyme is 2O2 with no observable superoxide as confirmed by EPR spin trapping experiments. This behaviour is different from hFMO3, that is shown to form both H2O2 and superoxide anion radical as a result of ～50% uncoupling. These data are consistent with the higher stability of the hFMO1 intermediate in comparison to hFMO3. Taken together, these data demonstrate the different behaviours of these two closely related enzymes with consequences for drug metabolism as well as possible toxicity due to reactive oxygen species.

Tamoxifen stimulates calcium entry into human platelets

The anti-estrogenic drug tamoxifen, which is used therapeutically for treatment and prevention of breast cancer, can lead to the development of thrombosis. We found that tamoxifen rapidly increased intracellular free calcium [Ca]i in human platelets from